Anatomical proximity of the inlet of the respiratory and digestive systems, along with the dual function of the pharynx as both airway and gastrointestinal passage, predisposes the lung to the dangers of aspiration during swallowing and retrograde transit of gastric content through the esophago-pharyngeal lumen. A large number of pulmonary and aerodigestive tract disorders, ranging from asthma, aspiration pneumonia, and other lung injuries to benign inflammatory lesions of the larynx and aerodigestive tract are attributed to the deleterious effects of the gastric content or its misdirection into the respiratory system The central theme of this program project therefore is mechanisms of upper gut and airway interaction with special emphasis on airway protection against aspiration. This theme is pursued in adult and infant humans and a feline model by systematic approach at 4 levels a) physiology b) pathophysiology c) diagnosis d) management. It uses the lessons learned from the studies of last funding period and is supported by the preliminary studies A total of 23 hypotheses will be tested in 6 specific aims. They systematically address different aspects of the central theme, answering different questions and providing a number of resolutions to a variety of important unresolved clinical uncertainties. The current proposal has three projects and an administrative core. In addition to long term professional relationship and research collaborations among the leadership of this project, each leader is an experienced investigator and has an established record of productivity and acknowledged contribution to their respective field. These fields include gastrointestinal physiology, neonatalogy, aerodigestive physiology, gastroenterology, otolaryngology, Gl motility and endoscopy. The degree of collaboration and cohesiveness of the three research teams is evidenced by the publication of the last funding period and the collaborative effort rendered by all in developing the current proposal and its preliminary data.